Aortic Graft Infection Secondary to Iatrogenic Transcolonic Graft Malposition.
Aortic graft infections are a rare but devastating complication of aortic revascularization. Often infections occur due to contamination at the time of surgery. Iatrogenic misplacement of the limbs of an aortobifemoral graft is exceedingly rare, and principles of evaluation and treatment are not well defined. We report 2 cases of aortobifemoral bypass graft malposition through the colon. Case 1 is a 54-year-old male who underwent aortobifemoral bypass grafting for acute limb ischemia. He had previously undergone a partial sigmoid colectomy for diverticulitis. Approximately 6 months after vascular surgery, he presented with an occult graft infection. Preoperative imaging and intraoperative findings were consistent with graft placement through the sigmoid colon. Case 2 is a 60-year-old male who underwent aortobifemoral bypass grafting due to a nonhealing wound after toe amputation. His postoperative course was complicated by pneumonia, bacteremia thought to be secondary to the pneumonia, general malaise, and persistent fevers. Approximately 10 weeks after the vascular surgery, he presented with imaging and intraoperative findings of graft malposition through the cecum. Aortic graft infection is usually caused by surgical contamination and presents as an indolent infection. Case 1 presented as such; Case 2 presented more acutely. Both grafts were iatrogenically misplaced through the colon at the index operation. The patients underwent extra-anatomic bypass and graft explantation and subsequently recovered.


Clinical aspects of otosclerotic ossicular chain fixations.
Otosclerosis is a human-specific ear disease characterised by complex bone-remodelling with multifactorial aetiology. It affects the bony labyrinth capsule and consequently fixates the stapes to the oval window rim. The fixation of the ossicular chain leads to a decrease in the middle ear's acoustic impedance-fitting and amplifier function that leads to conductive hearing loss. The process is progressive and when it involves the inner ear structures, it deteriorates the sensorineural function as well. The course of the illness can be prevented or delayed if hearing reconstructive surgery is performed on time. The development of stapes surgery spans the 20th century, and despite the major surgical steps - laid down by Shea and Marquet in the 1960s - are quite conservative, fine adjustments are still being made mainly due to technical progress. Several studies confirm that stapedotomy remained the first-to-offer therapeutic option in otosclerosis. With an adequate surgical technique, significant improvement can be achieved in the air conduction threshold, the air-bone gap may be minimalized or ceased over the speech frequencies, which significantly improves the quality of life of the patients. In this quest, we reviewed the Hungarian and the international literature as well in context with otosclerosis, with special attention to the newest methods in diagnostics and treatment management. Orv Hetil. 2020; 161(19): 780-788.


Expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed small cell lung cancer.
The transformation of epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) into small cell lung cancer (SCLC) accounts for 3-14% of the resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). At present, there is no relevant research to explore the dynamic expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed SCLC/neuroendocrine carcinoma (NEC). Genetic analysis and protein level analysis by next-generation sequencing (NGS), Whole-exome sequencing (WES) and immunohistochemistry were performed to explore expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed SCLC. The research used three patient-derived organoids (PDOs) to explore the efficacy of combo [chemotherapy (chemo) plus TKI or bevacizumab] treatment. According to the subsequent treatment regimens after SCLC/NEC transformation, 35 patients were divided into chemo (n=21) and combo (n=14) groups. EGFR L858R and EGFR E746-750 del protein expression by immunohistochemistry was 80.0% (4/5) and 100% (6/6), respectively (P=0.455) in initially-transformed tissues. Meanwhile, EGFR-mutant proteins were expressed in 85.7% (6/7) of dynamic rebiopsy tissues or effusion samples after the first transformation. Then, by the pathway enrichment analysis of tissue and plasma NGS, the EGFR-related pathways were still activated after SCLC/NEC transformation. Moreover, WES analysis revealed that transformed SCLC shared a common clonal origin from the baseline LUAD. The drug sensitivity of three PDOs demonstrated potent anti-cancer activity of EGFR-TKIs plus chemo, compared with chemo or TKI alone. There were significant differences in objective response rate (ORR) between the combo and chemo groups [42.9 % vs. 4.8%, P=0.010, 95% confidence interval (CI): 1.5-145.2]. Furthermore, the median post-transformation progression-free survival (pPFS) was significantly prolonged in the combo group, with 5.4 (95% CI: 3.4-7.4) versus 3.5 (95% CI: 2.7-4.3, P=0.012) months. EGFR 19del or L858R-mutant proteins could be constantly expressed, and EGFR pathway still existed in EGFR-mutant transformed SCLC/NEC with a common clonal origin from the baseline LUAD. Taking together, these molecular characteristics potentially favored clinical efficacy in transformed SCLC/NEC treated with the combo regimen.


Influence of nitrous oxide on motor-evoked potentials.
Rabbits were used as an experimental model in the study of motor-evoked potentials. To evaluate the effect of nitrous oxide on motor-evoked potentials while monitoring direct muscle and spinal cord responses. Motor-evoked potential monitoring provides a promising tool for intraoperative assessment of descending pathways function. However, to date, this technique is still at an experimental stage, since its routine use is mainly limited because of intraoperative recording difficulties caused by the influence of anesthesia. Eight male rabbits weighing between 3000 g and 3500 g were studied. Motor-evoked potentials were recorded from the extremity muscles and from the epidural space of the thoracic cord in response to electrical stimulation of the motor cortex at baseline conditions and at increasing nitrous oxide concentrations (10-70 vol%). The authors found a major suppressive effect of high nitrous oxide concentrations on the electromyographic responses. With 50 vol% nitrous oxide, electromyographic amplitudes were suppressed to 46% (fore leg) and 14% (hind leg) of the baseline values, whereas latencies did not change significantly. In contrast to muscular activity, spinal evoked responses representing neural activity were not affected by any concentration of nitrous oxide. Intraoperative monitoring of descending pathways by means of motor-evoked potentials during anesthesia of the rabbits based on nitrous oxide is feasible when neural activity is evaluated. Higher doses of nitrous oxide, however, are not compatible with recording of muscular activity.


Relic pleistocene permafrost, Western arctic, Canada.
Icy layers and interbedded frozen sediments along the Arctic Coastal Plain of northwestern Canada have been subjected to glacial deformation. Radio-carbon dates indicate that the deformation took place more than 40,000 years ago.


HIV, Hepatitis C, TB, Harm Reduction, and Persons Deprived of Liberty: What Standards Does International Human Rights Law Establish?
HIV, hepatitis C virus (HCV), and TB in prisons and other places of detention are serious public health concerns, with prevalence and incidence considerably higher than in the general community because of the overrepresentation of risky behavior, substandard conditions, overcrowding, people who inject drugs, and the wholly inadequate prevention, care, and treatment of these conditions, including the denial of harm reduction services. This is not only a severe public health crisis but also a serious human rights concern. This article works to clarify the standards established by human rights law with regards to HIV, HCV, TB, and harm reduction in prisons by examining international and regional case law, minimum standards on the treatment of prisoners and public health, as well as the work of UN treaty bodies, Special Rapporteurs, and prison monitoring bodies. It is imperative that urgent steps are taken to close the gap between human rights and public health standards on the one hand, and effective implementation in prison settings on the other.


Perturbation of nucleosome core structure by the SWI/SNF complex persists after its detachment, enhancing subsequent transcription factor binding.
To investigate the mechanism of SWI/SNF action, we have analyzed the pathway by which SWI/SNF stimulates formation of transcription factor-bound nucleosome core complexes. We report here that the SWI/SNF complex binds directly to nucleosome cores and uses the energy of ATP hydrolysis to disrupt histone/DNA interactions, altering the preferred path of DNA bending around the histone octamer. This disruption occurs without dissociating the DNA from the surface of the histone octamer. ATP-dependent disruption of nucleosomal DNA by SWI/SNF generates an altered nucleosome core conformation that can persist for an extended period after detachment of the SWI/SNF complex. This disrupted conformation retains an enhanced affinity for the transcription factor GAL4-AH. Thus, ATP-dependent nucleosome core disruption and enhanced binding of the transcription factor can be temporally separated. These results indicate that SWI/SNF can act transiently in the remodeling of chromatin structure, even before interactions of transcription factors.


Ultrasonographic changes of labrum morphology in patients with developmental dysplasia of the hip: a preliminary report on 74 dysplastic and unstable hips.
The aim of the study was to verify the labrum's morphological changes in unstable and dysplastic hips during treatment. Between January 2013 and April 2015, 74 dysplastic hips were divided into type D (n=12), type III (n=40), and type IV (n=22). The labrum was evaluated on ultrasonography (US) for echogenicity and dimensions with interobserver/intraobserver tests: test 1 (US at diagnosis and control group), test 2 (US at diagnosis and 6 weeks post-treatment), and test 3 (US at diagnosis and at end of treatment). Statistical analysis was performed. The labrum was less echogenic in test 1 and more echogenic in test 3, and the labrum was smaller in test 1 and larger in test 3. The labrum undergoes statistically significant increase of echogenicity and dimensions after treatment, suggesting a stabilizing role. Level of Evidence: Level II, Oxford Center for Evidence-based Medicine.


Differentiating protein-coding and noncoding RNA: challenges and ambiguities.
The assumption that RNA can be readily classified into either protein-coding or non-protein-coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger RNAs (mRNAs), and readily distinguished from the small number of well-characterized non-protein-coding RNAs (ncRNAs), such as transfer, ribosomal, and spliceosomal RNAs. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between mRNAs and ncRNAs both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some ncRNAs may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some RNAs can function both as mRNAs and intrinsically as functional ncRNAs, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an RNA unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the RNA level and to encode proteins suggests a false dichotomy between mRNAs and ncRNAs. Therefore, the functionality of any transcript at the RNA level should not be discounted.


Speech therapist led voice clinic: which patients may be suitable?
Joint Voice clinics run by an ENT surgeon (Laryngologist) and Voice therapist avoid repetition of clinical assessment, better planning of patient management and early initiation of treatment. Although is perceived as optimal management of voice patients it is perhaps not necessary for all patients as it is time consuming for the clinicians involved. The aim of this study was to investigate whether it was possible to identify any subgroup of patients that could potentially be seen in a Voice therapist-led new patient clinic by reviewing the outcome of 96 patients referred to a Joint Voice clinic. Forty-four patients were referred for voice therapy out of which 13 (30%) were teachers or lecturers (total number: 16 (81%)). Two others in this subgroup required medical treatment and the other surgery. The most common aetiology in these professional voice users was muscle tension dysphonia (10 patients, 63%). It is concluded that experienced Voice therapists appropriately trained in laryngostroboscopic assessment could potentially receive and manage direct referrals from primary care physicians. They should however work as part of a multi-professional Voice Disorders Team where the patients could be reviewed by an ENT surgeon if necessary. This would significantly improve the patient pathway for these patients, be cost-effective and make the best use of therapist's and ENT surgeon's time.


The future of Helicobacter pylori eradication: a personal perspective.
Future changes in the use of Helicobacter pylori eradication therapy first will involve a decision-making process to determine which individuals require testing. Clearly, only persons who require therapy need to be diagnosed and, at present, the indications for therapy are constantly expanding. The author takes the view that everyone with H. pylori would be better off without the bacterium, but accepts that in many countries resources are inadequate to achieve this goal. Where antibiotic therapy for H. pylori fails due to a resistant organism, second treatment must include a different class of antibiotic. When a third therapy is contemplated, antibiotic sensitivity studies are usually necessary. In developing counties where reinfection with H. pylori is common, lesser goals than permanent cure might be appropriate. Thus, selected patients could have H. pylori suppressive therapy to prevent full expression of H. pylori-associated disease, or to prevent reinfection after an initial eradicative therapy. After considering all these alternatives, one must conclude that a vaccination strategy, if safe and cost effective, is the ideal future therapy.


CD34 positive selection as prophylaxis against graft versus host disease in allogeneic peripheral blood stem cell transplantation.
We report our experience of CD34 positive selection as a means of graft T-cell depletion (TCD) in 14 consecutive HLA-identical Peripheral blood stem cells (PBSC) allografts as prophylaxis against graft versus host disease (GVHDp). CD34 positive selection was performed by immunomagnetic separation achieving a median CD34 and T-cell dose of 4.17 (range 1.4-8.50) x 10(6)/kg and 1.89 (range 0.92-13.18) x 10(4)/kg, respectively, in the graft. This represents 4-log depletion of T-cells. The median time to achieve a neutrophil count of 0.5 x 10(9)/l was 15 days and to achieve a platelet count of 50 x 10(9)/l was 20 days. Only four patients developed acute GVHD at a median of 41 days but this was exclusively mild grade I cutaneous disease and settled with oral steroids. Four patients, all of whom had AML, relapsed or progressed after transplant at a median of 161 (range 109-311) days. One of these had been transplanted in early relapse (9% blasts) whilst another was in second remission. The remaining 10 patients are alive and well. The median progression free survival for the whole population is 69% at 686 days. We conclude that CD34 positive selection by immunomagnetic separation in HLA-identical PBSC allografting achieves significant TCD with clinically trivial acute GVHD, prompt engraftment and an acceptable disease relapse risk.


Integration of the cognitive knowledge of activity in a service oriented architecture in the home care context.
The complex nature of a home care (HC) situation induces an important need for cooperation between the health care professionals. But even if this need is sometimes evocated in reports on HC issues, it is more difficult to get precise knowledge on this cooperative activity, and, consequently, propositions for computerized HC organization and management systems. We did some researches on this topic area. Previous phases of work let us highlight the actual need for cooperation, and obtain precise information on the HC activity processes and data. In this paper, we focused on the integration of this cognitive knowledge on the design of a HC cooperation architecture. Different levels of requirements for the cooperative system are mentioned: coordination, communication of information, delegation of activity, integration of services and personal access to the tasks to perform. A description of the usefulness and use of the cognitive knowledge is proposed, the architecture design, modular, distributed, and able to integrate external services is presented, and the results of a validation test of the implemented prototype, performed with actual HC professionals in an evaluation laboratory are presented.


Orientation Inside Linear Nests by Male and Female Osmia bicornis (Megachilidae).
Numerous species of solitary bees and wasps build linear nests with only one entrance. Developing insects must orient themselves inside their nest to choose the correct direction in which to emerge. Misorientation and chewing towards the dead end of the nest can result in significant mortality. Most insects position themselves towards the nest entrance during cocoon construction; however, some individuals are misoriented. We tested whether imagines can examine and possibly correct their orientation after emerging from their cocoons. Males were usually able to correct their misoriented position based on the shape of the cell wall and emerged through the correct entrance, whereas most females pursued the direction that they faced in their cocoons. We suggest that there can be more than one time point during development when bees can control their position in relation to the nest entrance and that the importance of these time points varies between sexes.


Role of peripheral pooling in porcine Escherichia coli sepsis.
In anesthesized pigs the effects of E. coli (2 X 10(8)/kg) on hemodynamics and red cell distribution were studied. After injection of 99m-Tc red cells (15 mCi), regional radioactivity was followed during 3 hours. Gated bloodpool studies were performed to measure end-diastolic volumes (EDV). Escherichia coli E. coli was infused in 14 pigs, while 7 animals served as controls. E. coli resulted in an early increase in pulmonary arterial pressure. Systemic arterial pressure decreased gradually, while cardiac output did not change significantly. The gated studies revealed that especially left ventricular end-diastolic volume (LVEDV) declined, to 50% of the basal value. Regional radioactivity did not change over lungs, liver and abdomen. Splenic activity declined markedly. Over the hindlimb a significant increase (29 +/- 8%) was observed. It is concluded that E. coli infusion in pigs induces a hemodynamic pattern similar to human sepsis. The decrease in LVEDV is probably related to peripheral pooling and a change in right ventricle (RV) performance.


Waterbowls: Reducing Impacting Droplet Interactions by Momentum Redirection.
Superhydrophobic surfaces can dramatically reduce the transport of mass or energy from impacting droplets by making them bounce off. Such transport processes are dependent on both the contact time and the contact area between the drop and the surface. To reduce transport, recent studies have focused on reducing the contact time. However, the contact area, which is dictated by the conformal spreading of the droplet, remains large, thereby limiting the reduction in the overall transport. Here, we show how surfaces can be designed to redirect the momentum of the spreading lamella causing it to lift off into 3-dimensional shapes, thereby dramatically reducing the contact area. We design superhydrophobic surfaces with an in-plane discontinuity leading to the accumulation of vertical momentum resulting in the out-of-plane ejection of the lamella into water bowls. We demonstrate a 2-fold reduction in the heat transfer between a cold rain and a warm surface. These insights can be broadly applied to other transport phenomena involving mass and energy exchange to limit heat loss under precipitation, icing of surfaces, reduce salt deposition on a surface exposed to ocean spray, or inhibit the formation of a water film on wings or wind turbine blades.


Diagnosis and management of pancreatic trauma.
The diagnosis and management of 76 patients with pancreatic trauma is reviewed. There was an overall mortality rate of 5 per cent. A preoperative serum amylase determination was a valuable parameter when assessing blunt trauma. Operative management required debridement and external drainage in approximately three-fourths of all injuries. Pancreatic resection was reserved for ductal disruption. Interruption of ductal integrity accounted for 47 per cent of all complications. Only one-third required reoperative therapy. Associated major vascular injuries accounted for all deaths.


Phase separation property of a hydrophobic deep eutectic solvent-water binary mixture: A molecular dynamics simulation study.
Over the past decade, deep eutectic solvents (DESs) have earned applicability in numerous fields as non-flammable, non-volatile, and greener alternatives to conventional organic solvents. In a first of its kind, a hydrophobic DES composed of a 1:1 mixture of oleic acid and lidocaine was recently reported, possessing a lower critical solution temperature in water. The thermoreversible phase property of this DES-water system was utilized to sequester out dye molecules from their aqueous solutions. In this article, we explore the phase separation phenomena for this particular DES in its aqueous solution using an all-atom molecular dynamics simulation. A 50 wt. % solution of the DES in water was studied at three different temperatures (253, 293, and 313 K) to understand the various molecular interactions that dictate the phase segregation property of these systems. In this work, we have elaborated on the importance of hydrogen bonding interactions and the non-bonding interactions between the components and the competition between the two that leads to phase separation. Overall, we observe that the increase in unfavorable interaction between the DES components and water with increasing temperature determines the phase separation behavior. We have also studied the modification in the dynamical properties of water molecules close to the phase boundary. Such molecular insights would be beneficial for designing novel solvent systems that can be used as extraction-based media in industries.


Gonadotropin gene expression and secretion in gonadotropin-releasing hormone antagonist-treated male rats: effect of sex steroid replacement.
The possibility of direct pituitary effects of sex steroids on gonadotropin gene expression and synthesis was studied in male rats. The animals were treated with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Org 30276; 0.5 mg/kg BW, sc, twice daily) for 10 days. Groups of the antagonist-treated rats were implanted at the beginning of the injections with Silastic capsules containing testosterone (T), 5 alpha-dihydrotestosterone (DHT), or diethylstilbestrol (DES). Groups treated with the antagonist alone or vehicle served as controls. The antagonist treatment decreased unoccupied pituitary receptors of GnRH by 93% (P less than 0.001), serum LH by 34% (P less than 0.01), and serum FSH by 30% (P less than 0.05), and serum T became undetectable (less than 0.10 nmol/liter). Compared to antagonist treatment alone, no further effects on serum or pituitary LH levels found after steroid replacements. In contrast, the antagonist-induced decreases in serum and pituitary FSH (30% and 70%, respectively; P less than 0.05-0.01) were totally reversed by the T and DHT implants, but not by DES. Pituitary levels of the LH beta-subunit mRNA were decreased by 60% (P less than 0.01) after antagonist treatment. Combination treatment with androgens had no further effect on this mRNA, whereas DES partially reversed this suppression (P less than 0.05). In contrast, the pituitary mRNA level of the FSH beta-subunit, which decreased with antagonist treatment by 90% (P less than 0.01), returned to the control level with T and DHT replacements, but only partially with DES. The pituitary mRNA level of the common alpha-subunit was significantly suppressed only by combined antagonist plus DHT treatment (P less than 0.01). However, combination of DES with the antagonist increased alpha-subunit mRNA levels 2.4-fold (P less than 0.05) compared to antagonist treatment alone. It is concluded that the suppression of gonadotropin secretion by GnRH antagonist treatment is accompanied in male rats by a parallel reduction in mRNA levels of the gonadotropin beta-subunits. Sex steroid replacement of the antagonist-treated animals selectively reverses some of the mRNA changes. Androgens (T and DHT) increase the mRNA of FSH beta-subunit, but have no effect on the LH beta-subunit. Estrogen increases the mRNA levels of common alpha- and LH beta-subunits and slightly increases that of FSH beta.(ABSTRACT TRUNCATED AT 400 WORDS)


Antipsychotic treatment and mortality in schizophrenia.
It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view. We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 (N = 1230). Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010. Compared with age- and gender-matched controls from the general population (N = 214920), the highest overall mortality was observed among patients with no antipsychotic exposure (hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3), ie, 0.0 defined daily dose (DDD)/day, followed by high exposure (>1.5 DDD/day) group (HR = 5.7, 5.2-6.2), low exposure (<0.5 DDD/day) group (HR = 4.1, 3.6-4.6), and moderate exposure (0.5-1.5 DDD/day) group (HR = 4.0, 3.7-4.4). High exposure (HR = 8.5, 7.3-9.8) and no exposure (HR = 7.6, 5.8-9.9) were associated with higher cardiovascular mortality than either low exposure (HR = 4.7, 3.7-6.0) or moderate exposure (HR = 5.6, 4.8-6.6). The highest excess overall mortality was observed among first-episode patients with no antipsychotic use (HR = 9.9, 5.9-16.6). Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.


Optimization of spectral coverage in an eight-cell oscillator-amplifier dye laser pumped at 308 nm.
Optimization of dye spectral range with a pulsed dye laser pumped by an XeCl excimer laser is described. The dyes were tested in an eight-cell oscillator-amplifier dye laser which is also described. Several solvents and mixtures of dyes were used for continuous coverage over 335-910-nm range. An additive to the solvent prevented deposits on the inside of the dye cells. The emitted wavelength can be extended to the UV by second harmonic generation. An achromatic device for separating the UV from the fundamental wavelength without beam displacement is described.


Imperforate hymen with elevated serum CA 125 and CA 19-9 levels.
To report the clinical characteristics of 14 patients with imperforate hymen and their levels of tumor markers (CA 19-9 and CA 125). Fourteen patients with imperforate hymen who followed-up between September 2006 and September 2010 in the Department of Obstetrics and Gynecology, Dicle University School of Medicine, Diyarbakir, Turkey, were evaluated retrospectively. The clinical features and the management of the patients are discussed. The mean age of the patients was 13.8 years. All patients had primary amenorrhea and pelvic pain. The most common clinical symptoms were cryptomenorrhea in 14 patients, pelvic pain in 11, palpable abdominal mass in 6, voiding difficulties in 7, and defecation problems in 2. In 6 patients with palpable pelvic mass, the mean + standard deviation values of tumor markers were as follows: CA 125, 84.0 +/- 23.7 and CA 19-9, 162 +/- 189. One week after surgery we measured CA 125 and CA 19-9 levels once again. The postoperative mean CA 125 level was 13.8 +/- 3.6, and the mean postoperative CA 19-9 level was 17.5 +/- 3.5. Preoperative levels of CA 125 and CA 19-9 were significantly higher than those of the postoperative period (p < 0.001 for both comparisons). Six patients were treated by T-shaped incision and 8 patients by a central surgical incision through the hymenal membrane. Diagnosis of imperforate hymen is very important before undergoing surgery in a different clinic. Many patients have seen several doctors before receiving a clear diagnosis and have had tumor markers evaluated because the presence of pelvic mass in patients suggests the possibility of a gynecologic malignancy. Imperforate hymen is one of the benign conditions that increase serum CA 125 and CA 19-9 levels and which is not listed in the classical medical textbooks. These markers are not needed for the diagnosis.


Reduced TRPC6 mRNA levels in the blood cells of patients with Alzheimer's disease and mild cognitive impairment.
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay. We found a specific reduction of TRPC6 mRNA levels in four AD sets and one MCI set. The median TRPC6 mRNA levels were lower in the following: (1) combined AD patients than in age-matched controls (0.78 vs 1.73, P<0.001); (2) mild-to-moderate AD patients than in age-matched controls (0.81 vs 1.73, P<0.001); and (3) MCI patients than in age-matched controls (0.76 vs 1.72, P<0.001). In the receiver-operating characteristic curve analysis, the area under curve was 0.85 for combined AD, 0.84 for mild-to-moderate AD and 0.79 for MCI. In a subgroup of AD patients with brain Aβ examination, TRPC6 was associated with standardized uptake value ratio of Pittsburgh Compound B (Spearman's r=-0.49, P=0.04) and cerebrospinal fluid Aβ42 (Spearman's r=0.43, P=0.04). The TRPC6 reduction in AD patients was further confirmed in blood RNA samples from The Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging, in post-mortem brain tissues from The Netherlands Brain Bank and in induced pluripotent stem cells-derived neurons from Chinese donors. We conclude that TRPC6 mRNA levels in the blood cells are specifically reduced in AD and MCI patients, and TRPC6 might be a biomarker for the early diagnosis of AD.


Inhibition of Adipogenesis by Oligonol through Akt-mTOR Inhibition in 3T3-L1 Adipocytes.
Polyphenols have recently become an important focus of study in obesity research. Oligonol is an oligomerized polyphenol, typically comprised of catechin-type polyphenols from a variety of fruits, which has been found to exhibit better bioavailability and bioreactivity than natural polyphenol compounds. Here, we demonstrated that Oligonol inhibits 3T3-L1 adipocyte differentiation by reducing adipogenic gene expression. During adipogenesis, Oligonol downregulated the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα), and δ (C/EBPδ) in a dose-dependent manner and the expression of genes involved in lipid biosynthesis. The antiadipogenic effect of Oligonol appears to originate from its ability to inhibit the Akt and mammalian target of rapamycin (mTOR) signaling pathway by diminishing the phosphorylation of ribosomal protein S6 kinase (p70S6K), a downstream target of mTOR and forkhead box protein O1 (Foxo1). These results suggest that Oligonol may be a potent regulator of obesity by repressing major adipogenic genes through inhibition of the Akt signaling pathway, which induces the inhibition of lipid accumulation, ultimately inhibiting adipogenesis.


Cu2O/PEDOT:PSS/ZnO Nanocomposite Material Biosensor for Esophageal Cancer Detection.
A highly sensitive photoelectrochemical (PEC) biosensor without external bias was developed in this study. The biosensor was configured with a p-Cu2O and n-ZnO heterostructure. Hexamethylenetetramine (HMTA) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was used to improve the crystal structure of Cu2O and ZnO and reduce the defects in the Cu2O/ZnO interface. This fabrication method provided the highly crystallized Cu2O/ZnO structure with excellent electrical property and photoresponse in visible light. The structure was applied to a biosensor for detecting two different cancerous levels of esophageal cells, namely, OE21 and OE21-1, with a high gain in photocurrent (5.8 and 6.2 times, respectively) and a low detection limit (3000 cells in 50 μL). We believe that such a p-n heterojunction PEC biosensor could advance biosensor development and provide a promising candidate for biomedical applications.


Reporting and classification of patient safety events in a cardiothoracic intensive care unit and cardiothoracic postoperative care unit.
The objective was to evaluate a new mechanism for reporting and classifying patient safety events to increase reporting and identify patient safety priorities. A voluntary patient safety event reporting system accessible by all health care workers was implemented in the Cardiothoracic Intensive Care and Post Anesthesia Care Units. Information collected included patient identifiers; date, time, and location of report and event; type and description of event; and severity score. Narrative descriptions of events were analyzed and coded to describe when in the care process the event occurred, what occurred, and a causal classification of why the event occurred. A total of 163 reports describing 157 events were received. These included 121 events reported from the intensive care unit (25.3 reported events per 1000 patient-days), a 3-fold increase compared with the preexisting on-line reporting system. A total of 113 reports (69%) came from nurses, 31 from physicians (19%), and 10 from other staff (6%). A majority of events (85, 54%) reached the patient but caused no harm. Multiple causes were identified for the majority of events. The most frequent causes were related to human factors (48%) and organizational factors (34%). Health care workers were willing to use the patient safety event reporting system, which yielded a broad range of patient safety data. Patient safety events are multifaceted and often have multiple causal factors. Application of a causal classification model for patient safety event coding in the intensive care and preoperative and postoperative care units is feasible and facilitates local communication of important event-related information.


Substance P is a promoter of adult neural progenitor cell proliferation under normal and ischemic conditions.
Neurogenesis continues throughout the life of mammals in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus (DG) of the hippocampus. The authors tested the potential of the neuropeptide substance P (SP) acting via the neurokinin-1 receptor (NK1R) in promoting the proliferation of adult rat neural progenitor cells (NPCs). Focal ischemia was induced in spontaneously hypertensive rats by transient middle cerebral artery occlusion. Substance P and the NK1R antagonist L-703,606 were infused into the lateral ventricles of rats by using Alzet osmotic minipumps. Progenitor cell proliferation was evaluated with immunostaining for bromodeoxyuridine (BrdU) and immature neural marker doublecortin (DCX). Neurospheres were cultured from the SVZ of adult rats. Under in vitro conditions, SP (0.01-10 micromol/L) increased the proliferation of cultured NPCs, with a peak increase of 52 +/- 7% at 0.1 micromol/L. Substance P (0.1 micromol/L) continuously increased NPC proliferation from 6 hours to 5 days, which was prevented by L-703,606 (by 69-98%). The cultured NPCs expressed both SP and NK1R proteins, indicating that these effects are receptor specific. Continuous infusion of SP (1 micromol/L) into the lateral ventricles for 5 days significantly increased the number of proliferating NPCs (cells positive for both BrdU and DCX) in both the SVZ (by 173 +/- 24%, p < 0.05) and DG (by 82 +/- 12%, p < 0.05) in adult rats; however, infusion of L-703,606 (10 micromol/L) significantly prevented the postischemic induction of NPC proliferation in both the SVZ (by 84 +/- 6%, p < 0.05) and DG (by 63 +/- 7%, p < 0.05). Data in these studies indicated that SP plays a role in normal and ischemia-induced neurogenesis in the adult brain and thus could help central nervous system plasticity following injury.


Psychometric properties of the German version of Observer OPTION5.
In order to conduct studies on shared decision-making (SDM) and to implement SDM in routine practice, psychometrically tested measures are needed. The development of the short 5-item version of the OPTION scale (Observer OPTION5) allows to assess SDM from an observer perspective. Observer OPTION5 is so far only available in English and Dutch. The aim of this study was to translate the Observer OPTION5 rating scale into German and to test its psychometric properties. The German Observer OPTION5 was tested in a secondary data analysis of audio-recordings of patient-physician-consultations (N = 79) in German primary care practices. Demographic data were analysed using descriptive statistics. To assess inter- and intra-rater reliability, intraclass correlation coefficients (ICCs) were calculated. For assessing concurrent validity, a correlation (Spearman's Rho) of the sum score of Observer OPTION5 and Observer OPTION12 was calculated. The consultations dealt with decisions regarding type 2 diabetes (N = 31), chronic back pain (N = 23), depression (N = 20), and other diseases (N = 5). Analysis of inter-rater reliability yielded an ICC of 0.82 for the sum score; across the five single items ICCs ranged between 0.45 and 0.77. For the intra-rater reliability an ICC of 0.83 was observed for the total score; across the five single items ICCs ranged between 0.45 and 0.86. The Observer OPTION5 had a mean total score of 11.84 (SD = 11.92) and the Observer OPTION12 had a mean total score of 10.3 (SD = 7.9), both on a potential range of 0 to 100. The correlation between the total scores of Observer OPTION5 and Observer OPTION12 was r = 0.47 (p = 0.01). The results regarding inter- and intra-rater reliability were excellent on the total score level. Observer OPTION5 showed moderate concurrent validity using Observer OPTON12. The results are generally comparable to the results of the original English version of Observer OPTION5. The German version of Observer OPTION5 can be used in research and evaluation of clinical practice. Nevertheless, further testing is adviced.


Hydatidiform mole in a scar on the uterus: A case report.
Cesarean scar molar pregnancy is extremely rare, but the incidence has been rising due to the continuous increase in the rate of cesarean section. The presence of a hydatidiform mole in the scar left on the uterus by the procedure may lead to severe complications. We performed a literature review and found only seven reported cases of cesarean scar molar pregnancy. Accurate diagnosis and appropriate treatment are extremely important for the patients' prognosis. A 35-year-old woman, gravida 4, para 1, complained of vaginal bleeding lasting more than 1 mo and amenorrhea lasting more than 2 mo. The patient's serum human chorionic gonadotropin was 4287800 IU/L. Ultrasound showed a 11.5 cm × 7.5 cm mass at the anterior lower wall of the uterus. The patient underwent suction evacuation, and partial grape-like tissue mixed with blood clots was removed. Uterine arterial embolization was performed to control intraoperative and postoperative bleeding. Histological examination confirmed the presence of a hydatidiform mole in uterine scar. After surgery, there was still a mass with heterogeneous intensity near the isthmus of the uterus on magnetic resonance imaging. The patient then underwent chemotherapy. During the 6-mo follow-up period, the mass disappeared and the serum human chorionic gonadotropin level gradually decreased to normal level. We report a case of cesarean scar molar pregnancy successfully cured by comprehensive treatment. We found that cesarean scar molar pregnancy was subject to intraoperative bleeding, and uterine arterial embolization before surgery may be helpful.


Postprandial metabolism of docosapentaenoic acid (DPA, 22:5n-3) and eicosapentaenoic acid (EPA, 20:5n-3) in humans.
The study of the metabolism of docosapentaenoic acid (DPA, 22:5n-3) in humans has been limited by the unavailability of pure DPA and the fact that DPA is found in combination with eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in natural products. In this double blind cross over study, pure DPA and EPA were incorporated in meals served to healthy female volunteers. Mass spectrometric methods were used to study the chylomicron lipidomics. Plasma chylomicronemia was significantly reduced after the meal containing DPA compared with the meal containing EPA or olive oil only. Both EPA and DPA were incorporated into chylomicron TAGs, while there was less incorporation into chylomicron phospholipids. Lipidomic analysis of the chylomicron TAGs revealed the dynamic nature of chylomicron TAGs. The main TAG species that EPA and DPA were incorporated into were EPA/18:1/18:1, DPA/18:1/16:0 and DPA/18:1/18:1. There was very limited conversion of DPA and EPA to DHA and there were no increases in EPA levels during the 5h postprandial period after the DPA meal. In conclusion, EPA and DPA showed different metabolic fates, and DPA hindered the digestion, ingestion or incorporation into chylomicrons of the olive oil present in the meal.


Caregiver sensitivity supported young children's vocabulary development during the Covid-19 UK lockdowns.
Previous studies have shown that caregivers' sensitive, responsive interactions with young children can boost language development. We explored the association between caregivers' sensitivity and the vocabulary development of their 8-to-36-month-olds during COVID-19 when family routines were unexpectedly disrupted. Measuring caregivers' sensitivity from home interaction videos at three timepoints, we found that children who experienced more-sensitive concurrent interactions had higher receptive and expressive vocabularies (N=100). Children whose caregivers showed more-sensitive interactions at the beginning of the pandemic showed greater expressive vocabulary growth six (but not 12) months later (n=58). Significant associations with receptive vocabulary growth were not observed. Our findings highlight the importance of sensitivity at a time when other positive influences on language development were compromised.


Identifying subtle functional change in individuals with mild cognitive impairment: development and validation of the Healthy Brain Ageing - Functional Assessment Questionnaire.
Accumulating research suggests that individuals with Mild Cognitive Impairment (MCI) experience subtle functional changes, but that available functional assessment tools are insensitive to this. To address this gap, we describe the development and validation of the self-report, "Healthy Brain Ageing Functional Assessment Questionnaire" (HBA-FAQ). We examined the factor structure and psychometric properties of the HBA-FAQ in 503 participants with normal cognition, subjective cognitive decline (SCD), MCI or dementia. Our results found the HBA-FAQ to have good reliability, validity and stronger discriminative ability between healthy control participants and those with SCD (0.734, p = .001), MCI (0.666, p = .012) and dementia (0.798, p < .001) compared to a widely-used instrumental activities of daily living screener. In conclusion, the HBA-FAQ is a valid, reliable self-report tool, providing an efficient and sensitive approach to identifying subtle changes in daily functioning in older people at risk of dementia.


Impact of metastatic lymph node ratio in node-positive colorectal cancer.
Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Presently, the most widely used staging system for CRC is the tumor nodes metastasis classification system, which classifies patients into prognostic groups according to the depth of the primary tumor, presence of regional lymph node (LN) metastases, and evidence of distant metastatic spread. The number of LNs with confirmed metastasis is related to the severity of the disease, but this number depends on the number of LNs retrieved, which varies depending on patient age, tumor grade, surgical extent, and tumor site. Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination. Hence, the impact of lymph node ratio (LNR), defined as the number of metastatic LNs divided by the number of LNs retrieved, has been investigated in various malignancies, including CRC. In this editorial, we review the literature demonstrating the clinicopathological significance of LNR in CRC patients. Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status. When the LNR is taken into consideration for survival analysis, the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor. The cut-off points for LNRs were proposed in numerous studies. However, optimal thresholds for LNRs have not yet received consensus. It is still unclear whether the LNR has more prognostic validity than N stage. For all these reasons, the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.


Cytoskeleton alteration correlates with gross structural plasticity in the cat lateral geniculate nucleus.
Monocular deprivation during early development causes rearrangement of neural connections within the visual cortex that produces a shift in ocular dominance favoring the non-deprived eye. This alteration is manifested anatomically within deprived layers of the lateral geniculate nucleus (LGN) where neurons have smaller somata and reduced geniculocortical terminal fields compared to non-deprived counterparts. Experiments using monocular deprivation have demonstrated a spatial correlation between cytoskeleton alteration and morphological change within the cat LGN, raising the possibility that subcellular events mediating deprivation-related structural rearrangement include modification to the neuronal cytoskeleton. In the current study we compared the spatial and temporal relationships between cytoskeleton alteration and morphological change in the cat LGN. Cross-sectional soma area and neurofilament labeling were examined in the LGN of kittens monocularly deprived at the peak of the critical period for durations that ranged from 1 day to 7 months. After 4 days of deprivation, neuron somata within deprived layers of the LGN were significantly smaller than those within non-deprived layers. This structural change was accompanied by a spatially coincident reduction in neurofilament immunopositive neurons that was likewise significant after 4 days of deprivation. Both anatomical effects reached close to their maximum by 10 days of deprivation. Results from this study demonstrate that alteration to the neuronal cytoskeleton is both spatially and temporally linked to the gross structural changes induced by monocular deprivation.


Subcritical wave instability in reaction-diffusion systems.
We report an example of subcritical wave instability in a model of a reaction-diffusion system and discuss the potential implications for localized patterns found in experiments on the Belousov-Zhabotinsky reaction in a microemulsion.


Multiple calcium mobilization pathways in single avian salt gland cells.
Agonist-induced changes in intracellular Ca2+ concentration ([Ca2+]i) in individual secretory cells from the avian salt gland were detailed using dual-wavelength microspectrofluorimetry of the Ca2(+)-sensitive fluorescent probe fura-2. Resting [Ca2+]i averaged 42 +/- 5 nM. Stimulation with the cholinergic agonist carbachol (1 microM) resulted in a rapid increase in [Ca2+]i to 308 +/- 26 nM, which was sustained at a nearly constant elevated level (328 +/- 31 nM) throughout agonist application. In the absence of extracellular Ca2+ or in the presence of an inorganic blocker of Ca2+ entry (Ni2+, 1 mM), only a transient increase in [Ca2+]i occurred on agonist stimulation, whereas subsequent readmission of Ca2+ or washout of Ni2+ reinitiated a sustained increase in [Ca2+]i. The initial transient response results from Ca2+ release from intracellular stores, whereas the sustained phase represents entry of extracellular Ca2+ into the cytoplasm. Repetitive stimulations in Ca2(+)-free medium alternating with Ca2(+)-containing medium were performed to examine the mechanisms involved in refilling of the agonist-sensitive intracellular pool. After depletion of the intracellular pool by stimulation in Ca2(+)-free medium, removal of the agonist and readmission of Ca2+ resulted in a rapid transient increase in [Ca2+]i that could be blocked by Ni2+, La3+, or elevated K+. Subsequent removal of extracellular Ca2+ and restimulation nonetheless showed that complete refilling of the intracellular pool had occurred in each case. These results suggest that two separate Ca2(+)-entry mechanisms, one sensitive to Ni2+, La3+, and elevated K+ and responsible for the agonist-induced increase in [Ca2+]i and one insensitive to the blockers and involved in refilling of the intracellular pool, may exist in salt gland cells. Spontaneous oscillations of [Ca2+]i that are independent of extracellular Ca2+ have also been observed in 10% of the cells. The abolition of the oscillations by depletion of the agonist-sensitive pool suggests this pool as the Ca2+ source for the oscillations.


Influence of Long-term Application of Feedlot Manure Amendments on Water Repellency of a Clay Loam Soil.
Long-term application of feedlot manure to cropland may increase the quantity of soil organic carbon (C) and change its quality, which may influence soil water repellency. The objective was to determine the influence of feedlot manure type (stockpiled vs. composted), bedding material (straw [ST] vs. woodchips [WD]), and application rate (13, 39, or 77 Mg ha) on repellency of a clay loam soil after 17 annual applications. The repellency was determined on all 14 treatments using the water repellency index ( index), the water drop penetration time (WDPT) method, and molarity of ethanol (MED) test. The C composition of particulate organic matter in soil of five selected treatments after 16 annual applications was also determined using C nuclear magnetic resonance-direct polarization with magic-angle spinning (NMR-DPMAS). Manure type had no significant ( > 0.05) effect on index and WDPT, and MED classification was similar. Mean index and WDPT values were significantly greater and MED classification more hydrophobic for WD than ST. Application rate had no effect on the index, but WDPT was significantly greater and MED classification more hydrophobic with increasing application rate. Strong ( > 0.7) but nonsignificant positive correlations were found between index and WDPT versus hydrophobic (alkyl + aromatic) C, lignin at 74 ppm (O-alkyl), and unspecified aromatic compounds at 144 ppm. Specific aromatic compounds also contributed more to repellency than alkyl, O-alkyl, and carbonyl compounds. Overall, all three methods consistently showed that repellency was greater for WD- than ST-amended clay loam soil, but manure type had no effect.


MiR-483-3p inhibition ameliorates myocardial ischemia/reperfusion injury by targeting the MDM4/p53 pathway.
MiR-483-3p is involved in the pathogenesis of acute myocardial infarctions, but its association with myocardial ischemia reperfusion (IR) remains mostly unknown. In this study, an in vitro model of myocardial IR injury was established by putting H9c2 cells into hypoxia reoxygenation (HR) treatment to explore the effects and possible mechanisms of miR-483-3p in myocardial IR injury. HR exposure resulted in increased miR-483-3p levels in H9c2 cells. MiR-483-3p was overexpressed or downregulated in H9c2 cells by transfection of miR-483-3p mimic or miR-483-3p inhibitor. In HR-treated H9c2 cells, MiR-483-3p mimics inhibited cell viability, promoted lactate dehydrogenase release, and increased apoptosis, but miR-483-3p inhibitors caused the opposite effects. MDM4 was verified to be the target mRNA of miR-483-3p and negatively modulated by miR-483-3p. MiR-483-3p inhibitor upregulated MDM4 and Bcl-2, but downregulated p53 and Bax in HR-treated H9c2 cells, whereas miR-483-3p overexpression produced the opposite effects.. Moreover, MDM4 siRNA transfection partially reversed the role of miR-483-3p inhibition in HR injury and p53 pathway inactivation of H9c2 cells. In summary, by targeting the MDM4/p53 pathway, miR-483-3p inhibition may alleviate myocardial HR injury. MiR-483-3p may be a potential therapeutic target of myocardial IR injury.


New Clinical Faculty Training Program: Transforming Practicing Dentists into Part-Time Dental Faculty Members.
At Indiana University School of Dentistry, a New Clinical Faculty Training (NCFT) program was created with the primary goals of informing new part-time faculty members of clinical policies and assessment guidelines and thus developing qualified and satisfied faculty members. The aim of this study was to determine if participation in the training program improved the participants' satisfaction and competence in comparison to their colleagues who did not participate in the program. Two cohorts were compared: a control group of part-time faculty members who did not receive formal training when they were hired (n=21; response rate 58.3%); and the intervention group, who had participated in the NCFT program (n=12; response rate 80%). A survey of faculty members in the control group gathered information on their experiences when initially hired, and a pretest was administered to measure their knowledge of clinical policies. After the control group was given an overview of the program, their feedback was collected through post surveys, and a posttest identical to the pretest was given that found statistically significant increases on questions one (p=0.003) and four (p=0.025). In February 2014, 15 new faculty members participated in the pilot implementation of the NCFT program. Of those 15, 12 (the intervention group) completed follow-up surveys identical to the pre survey used with the control group. Statistically significant differences were found for the factors clinical teaching (p=0.005) and assessment training (p=0.008) with better responses for the NCFT group. These results suggest that participation in the program was associated with improved clinical teaching knowledge and job satisfaction.


Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein.
Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and targeting, as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA manipulation and detection.


Prevalence of intestinal protozoans in French patients infected with HIV.
To assess the prevalence of intestinal protozoans in French HIV-infected patients, stool samples, duodenojejunal biopsies, and/or colorectal biopsies from 81 patients were studied for parasites, viruses, and bacteria. Pathogens were found in 70.6% of AIDS patients with diarrhea or malabsorption. The respective prevalence of protozoa in AIDS patients with diarrhea was Cryptosporidium sp.: 37.3%, Blastocystis hominis: 13.7%, Giardia intestinalis: 5.8%, Isospora belli: 2%, Enterocytozoon bieneusi: 2%. Microsporidia were noted in one patient with severe malabsorption but no diarrhea. Other pathogens included cytomegalovirus in 27.4% and Mycobacterium avium in 5.8%. Patients with identified pathogens were more immunosuppressed and more severely malnourished than those with unexplained diarrhea. Multiple pathogens were found in 13 of 81 patients (16%). Twenty-six of 66 identified pathogens (40%) were diagnosed only on biopsy specimens. Chronic diarrhea in HIV patients could be explained in the vast majority by appropriate gastrointestinal investigations. Cryptosporidia played a major role, while microsporidia appeared to be less common.


Development and verification of hardware for life science experiments in the Japanese Experiment Module "Kibo" on the International Space Station.
Japan Aerospace Exploration Agency (JAXA) has developed a cell biology experiment facility (CBEF) and a clean bench (CB) as a common hardware in which life science experiments in the Japanese Experiment Module (JEM known as "Kibo") of the International Space Station (ISS) can be performed. The CBEF, a CO2 incubator with a turntable that provides variable gravity levels, is the basic hardware required to carry out the biological experiments using microorganisms, cells, tissues, small animals, plants, etc. The CB provides a closed aseptic operation area for life science and biotechnology experiments in Kibo. A phase contrast and fluorescence microscope is installed inside CB. The biological experiment units (BEU) are designed to run individual experiments using the CBEF and the CB. A plant experiment unit (PEU) and two cell experiment units (CEU type1 and type2) for the BEU have been developed.


Short Tear Breakup Time Could Exacerbate the Progression of Presbyopia in Women.
The contributory factors and symptoms for presbyopia progression have not been fully determined. The purpose of the study was to compare presbyopia progression in subjects with short and normal tear breakup time and to explore the severity of common ocular symptoms associated with presbyopia progression. We conducted a clinic-based, retrospective, cross-sectional study. Inclusion criteria were bilateral phakic patients aged 40-69 years with best-corrected distance visual acuity better than 20/30, and exclusion criteria were the use of glaucoma eye drops, any disease affecting vision, or history of ocular surgery. We measured the binocular near add power and compared the results using Kaplan-Meier analysis. Association between near add power and ocular symptoms was explored. There were 1411 participants (mean age of 50.1 years). There were no significant differences in age, intraocular pressure, spherical equivalent, astigmatism, or anisometropia between the sexes. Kaplan-Meier analysis indicated that women with short tear breakup time reached the endpoint (near add power of +3.00 D) significantly earlier than those with normal tear breakup time (P = 0.043; Cox-Mantel test). Eye fatigue was most severe in the group with an add power of 1.25-2.00 D. Near add power was correlated with hyperopia, astigmatic errors, and anisometropia. This study suggests an exacerbation of presbyopia progression in women with short tear breakup time. Eye fatigue was most severe in those with an add power of 1.25-2.00 D.


Novel mechanisms of endothelial mechanotransduction.
Atherosclerosis is a focal disease that develops preferentially where nonlaminar, disturbed blood flow occurs, such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to disturbed flow compared with steady laminar flow. Disturbed flow that occurs in so-called atheroprone areas activates proinflammatory and apoptotic signaling, and this results in endothelial dysfunction and leads to subsequent development of atherosclerosis. In contrast, steady laminar flow as atheroprotective flow promotes expression of many anti-inflammatory genes, such as Kruppel-like factor 2 and endothelial nitric oxide synthase and inhibits endothelial inflammation and athrogenesis. Here we will discuss that disturbed flow and steady laminar flow induce pro- and antiatherogenic events via flow type-specific mechanotransduction pathways. We will focus on 5 mechanosensitive pathways: mitogen-activated protein kinases/extracellular signal-regulated kinase 5/Kruppel-like factor 2 signaling, extracellular signal-regulated kinase/peroxisome proliferator-activated receptor signaling, and mechanosignaling pathways involving SUMOylation, protein kinase C-ζ, and p90 ribosomal S6 kinase. We think that clarifying regulation mechanisms between these 2 flow types will provide new insights into therapeutic approaches for the prevention and treatment of atherosclerosis.


Recurrent Mixed Cryoglobulinemia Despite Sustained Virologic Response to Treatment: A Case Report.
Cryoglobulinemia is a manifestation of hepatitis C virus (HCV) infection. Treatment of HCV is the mainstay of therapy for mixed cryoglobulinemia syndrome, and newer HCV therapies with direct-acting antiviral agents have achieved great success in treating HCV infection compared with pegylated interferon alfa and ribavirin. Recurrence of mixed cryoglobulinemia syndrome following successful treatment with direct-acting antiviral agents is uncommon, and when it occurs, it is most often due to relapse of HCV viremia. We report a case of recurrent mixed cryoglobulinemia syndrome following HCV treatment with a new direct-acting antiviral agent (sofosbuvir) and ribavirin, in which HCV RNA was undetectable in serum, but detectable in the cryoprecipitate.


Demonstration of vasoproliferative activity from mammalian retina.
Vasoproliferative activity has been demonstrated in extracts of retinas from human, bovine, and feline sources. These retinal extracts are capable of stimulating (a) proliferation and thymidine uptake of bovine vascular endothelial cells in culture and (b) neovascularization on the chick chorioallantoic membrane. Extracts of skeletal muscle, cardiac muscle, and liver lack similar stimulatory activity. The activity is nondialyzable, stable at 56 degrees C, and inactivated at 100 degrees C. Retinal extracts stimulate the proliferation of corneal fibroblasts but have no effect on the proliferation of vascular smooth muscle cells. Indirect evidence suggests the liberation of a vasoproliferative factor from retina in several ocular disorders. The data in this report represent the first direct demonstration of vasoproliferative activity from mammalian retina.


Assessing the Use of Probes and Quenchers for Understanding the Reactive Species in Advanced Oxidation Processes.
Advanced oxidation processes (AOPs) are increasingly applied in water and wastewater treatment. Understanding the role of reactive species using probes and quenchers is one of the main requirements for good process design. However, much fundamental kinetic data for the reactions of probes and quenchers with reactive species is lacking, probably leading to inappropriate probe and quencher selection and dosing. In this work, second-order rate constants for over 150 reactions of probes and quenchers with reactive species such as •OH, SO4•-, and Cl• and chemical oxidants such as free chlorine and persulfate were determined. Some previously ill-quantified reactions (e.g., furfuryl alcohol and methyl phenyl sulfoxide reactions with certain chemical oxidants, nitrobenzene and 1,4-dioxane reactions with certain halogen radicals) were found to be kinetically favorable. The selection of specific probes can be guided by the improved kinetic database. The criteria for properly choosing dosages of probes and quenchers were proposed along with a procedure for quantifying reactive species free of interference from probe addition. The limitations of probe and quencher approaches were explicated, and possible solutions (e.g., the combination with other tools) were proposed. Overall, the kinetic database and protocols provided in this work benefit future research in understanding the radical chemistry in AOPs as well as other radical-involved processes.


A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family.
Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1 ) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The in-born errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intragenic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed.


[The catecholamine system in rat fetal brain with a disrupted corticosteroid balance].
The disturbance of corticosteroids balance of female rats on the 16 and 18 days of pregnancy by injections of exogenous corticosterone or methopyrone--blocker of endogenous hormone formation--decreased both body weight and activity of the rate-limiting catecholamine synthesising enzyme--tyrosine hydroxylase (TH) in the stem half of the 21 day fetal brain. Concomitantly with inhibitory action, which may be caused by general retardation of the organism development, corticosteroids stimulated TH activity during prenatal ontogenesis. Fetuses developed under elevated corticosteroid level had lower body weight but higher TH activity in comparison with fetuses endured the deficit of these hormones. Besides, corticosterone injection to the females on the 20th day of gestation increased in 6 hours TH activity in stem half of their fetus brain. The data obtained suggested the prominent role of corticosteroids in the prenatal development of brain catecholaminergic system.


[Preventive vaccines opposite to the virus of the human papilloma. A new hope against the cancer of the genital feminine tract].
One of the most relevant investigations on cancer during the past 25 years in the scientific community is the increasing knowledge about HPV infection and its ethiologic relationship with cervical cancer, even the most with persistent infection of specific genotypes of this virus. Worldwide, a woman dies from cervical cancer every 2 minutes. There are two potential concerns associated with vaccination: In the past we developed a secondary prevention programme, potentially based on screening. Now, vaccines have demonstrated a high grade of efficacy and security, specially when administered to pre-adolescents, and there will be a lower prevalence of the disease, as has already been shown in ongoing and completed trials, and secondary, avoidance of unnecessary diagnostic procedures and costs. In this evaluation we look forward to results on long-term vaccine efficacy and the possibility to make a pooled analysis on vaccine efficacy in preventing cervical cancer. Although some of us may not see it, we undoubtedly believe that we are close to the begining of the end of cervical cancer.


The patient/client/consumer/service user and medical ethics 40 years on.
This essay, written from my non-doctor's 'lay' perspective, sketches a gradually improving approach to medical ethics over the 40-year period since this journal was founded. A central feature of this improvement has been the increasing focus of medical ethics on the interests and perspectives of the patients/clients/consumers/service users, whose interests doctors and other healthcare workers serve. Events such as misuse of the end of life 'Liverpool Care Pathway' and the shockingly poor care revealed in National Health Service hospitals in Mid-Staffordshire show that these improvements are by no means universal. Nonetheless, there has been a steady improvement in general terms towards putting patients first and it is not flattery to say that in its consistent support for this concern and in its promotion of non-medical involvement in medical ethics education the Journal of Medical Ethics has itself made a significant contribution to 'doing good medical ethics'.


Tuft1 promotes thyroid carcinoma cell invasion and proliferation and suppresses apoptosis through the Akt-mTOR/GSK3β signaling pathway.
In this study, we aimed to investigate the biological functions of Tuftelin 1 (Tuft1) in thyroid carcinoma (TC) and determine its underlying molecular mechanism. We found that the expression of Tuft1 was significantly upregulated in TC tissues. Using TC tissue microarrays (n = 154), we found that Tuft1 expression was closely related with the overall survival (OS) and disease-free survival (DFS) of TC patients. Knockdown of Tuft1 in TPC-1 and SW579 cells suppressed the invasion and proliferation of TC cells and increased the apoptosis of TC cells. In vivo, knockdown of Tuft1 attenuated tumor growth and suppressed the phosphorylation of Akt, mTOR, and GSK3β signaling. Addition of recombinant Tuft1 protein (rTuft1) to TC cells increased the phosphorylation of Akt, mTOR, and GSK3β signaling. An mTOR inhibitor (Dactolisib) abrogated rTuft1 protein-induced TC cell invasion, proliferation, and apoptosis inhibition, whereas a GSK3β inhibitor (CHIR-98014) only abrogated rTuft1 protein-induced proliferation and apoptosis inhibition. These results suggest that Tuft1 promotes TC cell invasion and proliferation, and suppresses apoptosis through the Akt-mTOR or Akt-GSK3β signaling pathway. In the future, Tuft1 may serve as a potential therapeutic target for TC.


Signaling at the gliovascular interface.
Advances in fluorescent calcium indicating dyes over the past decade have identified calcium signaling as the tool by which astrocytes communicate among themselves and with neighboring neurons. Studies of astrocyte-neuron interactions have shown that calcium signaling is a potent modulator of the strength of both excitatory and inhibitory synapses. The concept that astrocytes possess a mechanism for rapid cell communication has not been incorporated, however, into the supportive functions of astrocytes. Because many of the classical tasks of astrocytes are linked to the blood-brain barrier, we have here examined the expression of proteins required for calcium signaling in their vascular end-foot processes. The gap junction protein, Cx43, was expressed intensively around the vessels interconnecting astrocytic end-foot processes. These gap junctions permitted diffusion of Lucifer yellow, specifically along the path of glial end feet apposed to the vessel wall. The purinergic receptors, P2Y(2) and P2Y(4), were also strongly expressed at the gliovascular interface and colocalized with GFAP around larger vessels in cortex. Multiphoton imaging of freshly prepared brain slices loaded with Fluo-4/AM revealed that ATP mobilized cytosolic calcium in astrocytic end feet, whereas electrical stimulation triggered calcium waves propagating along the vessel wall. Brain endothelial cells and pericytes were physically separated from astrocytes by the basal lamina and responded only weakly to ATP. These observations identify astrocytic end-foot processes plastered at the vessel wall as a center for purinergic signaling. It is speculated that calcium signaling may play a role in astrocytic functions related to the blood-brain barrier, including blood flow regulation, metabolic trafficking, and water homeostasis.


Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis.
A novel association between a single nucleotide polymorphism on chromosome 7p21.1 and large-vessel ischemic stroke was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed. We determined whether the lead single nucleotide polymorphisms were associated with asymptomatic carotid plaque (N=25 179) and carotid intima-media thickness (N=31 210) detected by carotid ultrasound in a meta-analysis of population-based and community cohorts. Immunohistochemistry was used to determine whether HDAC9 was expressed in healthy human cerebral and systemic arteries. In the Tampere Vascular Study, we determined whether HDAC9 mRNA expression was altered in carotid (N=29), abdominal aortic (N=15), and femoral (N=24) atherosclerotic plaques compared with control (left internal thoracic, N=28) arteries. Both single nucleotide polymorphisms (rs11984041 and rs2107595) were associated with common carotid intima-media thickness (rs2107595; P=0.0018) and with presence of carotid plaque (rs2107595; P=0.0022). In both cerebral and systemic arteries, HDAC9 labeling was seen in nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells. HDAC9 expression was upregulated in carotid plaques compared with left internal thoracic controls (P=0.00000103). It was also upregulated in aortic and femoral plaques compared with controls, with mRNA expression increased in carotid compared with femoral plaques (P=0.0038). Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. Further studies in experimental models are required to confirm this link.


Assessment of wheelchair drag resistance using a coasting deceleration technique.
To apply a recently developed coasting deceleration method to measure rolling and aerodynamic resistances opposing wheelchair propulsion on a variety of different wheelchairs and wheel combinations and on two different ground surfaces. For each condition, 20-25 trials were performed across a speed range of approximately 70-300 m/min. The least-squares method was then used to arrive at values for the coefficient of rolling resistance (CR) and effective frontal area of the wheelchair and occupant. Wheelchair rolling resistance was found to be velocity dependent under some circumstances. CR values on linoleum differed among folding lightweight wheelchairs and when compared with a rigid ultralight and racing wheelchair. Changing rear wheels and tires on one wheelchair resulted in a 14% difference in CR. Carpet increased CR values by an average of 0.0118 over the values determined on linoleum. As expected, effective frontal area of the wheelchair and occupant values were lower for the racer than for the folding lightweight wheelchair. Wheelchair rolling resistance is not always independent of velocity, and CR on linoleum can vary among wheelchairs by as much as seven-fold, and carpet can more than double CR.


Aging, confidence, and misinformation: recalling information with the cognitive interview.
In 2 experiments, younger and older adults witnessed a simulated robbery, received misleading information about the event, and then were interviewed with the Cognitive Interview about their memory for the robbery. In both experiments, older adults were disproportionately more confident than younger adults in the accuracy of incorrect information that they recalled than in the accuracy of correct information. Critically, this age-related increase in high-confidence errors occurred even in comparison with younger adults who were matched with older adults on the overall amount and accuracy of the information remembered about the robbery. In addition, Experiment 2 showed that retrieval warnings to disregard the misinformation were just as effective in older adults as compared with younger adults at reducing the reporting of misleading information. Finally, both experiments showed that across the multiple retrieval stages of the Cognitive Interview, the final retrieval stage is roughly half as effective for older adults relative to younger adults at eliciting previously unreported information. These results indicate that investigators have much less to gain from older adults than they do from younger adults with repeated inquiries (during the same session) about a witnessed event.


Latent hepatitis B virus (HBV) infection in systemic necrotizing vasculitis.
We have investigated hepatitis B virus (HBV) infection in systemic necrotizing vasculitis (SNV). Our approach included the detection of the viral surface antigen (HBsAg) with a radioimmunoassay employing monoclonal anti-HBs (m-RIA); in addition, HBV DNA was looked for in serum and peripheral mononuclear blood cells. Among 28 subjects with SNV, 12 were found to be positive for HBsAg with the conventional test (p-RIA) and 7 additional subjects had anti-HBc and/or anti-HBs. From the 16 HBsAg negative individuals, 9 had HBsAg epitopes identified in serum with the m-RIA test and 1 had a low amount of circulating viral DNA. In contrast, only 1 among 6 subjects with other systemic vasculitis showed a positive test for m-RIA and HBV DNA assays; this individual had acquired HIV infection through transfusions which were also probably the source of his HBV infection. HBV DNA sequences were identified in peripheral mononuclear blood cells of 9 from the 37 tested, including 2 individuals who were HBsAg positive only with m-RIA. Therefore, our study indicates a much higher rate of HBV infection in patients with polyarteritis nodosa than previously suspected.


Absolute Neutrophil Count and Mean Platelet Volume in the Blood as Biomarkers to Detect Lung Cancer.
Inflammation plays an extremely considerable role in the development and progression of malignancies. Absolute neutrophil count (ANC) and mean platelet volume (MPV) in blood are associated with various inflammatory conditions and resulted in independent prognostic factors for lung cancer. However, whether ANC and MPV can be diagnostic markers for lung cancer remains unknown. This retrospective study investigated the roles of ANC and MPV, either alone or combined, in diagnosing lung cancer. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People's Hospital Affiliated with Nanjing Medical University. The Mann-Whitney U-test was performed to compare differences between lung cancer patients and healthy individuals. Spearman's correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. 209 patients diagnosed with lung cancer and 236 healthy subjects were enrolled in this study. Levels of ANC and MPV increased in lung cancer patients compared with healthy individuals (P < 0.001). ANC had statistically significant negative weak correlation with albumin concentrations (r = -0.154, P = 0.026), and MPV had statistically significant negative weak correlation with total protein concentrations (r = -0.153, P = 0.027) in lung cancer patients. ANC and neutrophil-to-lymphocyte ratio had statistically significant positive correlation in both lung cancer patients (r = 0.756, P < 0.001) and healthy subjects (r = 0.639, P < 0.001). MPV and platelet-to-lymphocyte ratio had statistically significant negative weak correlation in both lung cancer patients (r = -0.242, P < 0.001) and healthy subjects (r = -0.325, P < 0.001). ANC had sensitivity (SEN) and specificity (SPE) of 0.512 and 0.809, respectively, and the area under the curve (AUC) with 95% confidence interval (95% CI) was 0.656 (0.603-0.710). SEN and SPE of MPV were 0.928 and 0.708, respectively, and the AUC (95% CI) was 0.913 (0.889-0.938). When ANC and MPV were combined, SEN and SPE became 0.842 and 0.835, respectively, and the AUC (95% CI) became 0.919 (0.895-0.943). Compared with ANC or MPV alone, the combination of ANC and MPV can improve diagnostic ability to distinguish lung cancer patients from healthy subjects.


[Hormonal therapy for prostate cancer: methods and prognosis].
To search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC). This study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles. The three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001). Compared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.


On the limitations of adiabatic population transfer between molecular electronic states induced by intense femtosecond laser pulses.
The possibility to perform a stimulated Raman adiabatic passage process in molecules on the ultrafast time scale is investigated theoretically. Motivated by recent experiments, the mid R:B<--mid R:X electronic transitions in molecular iodine are studied as a prototype example with the goal to selectively induce a population transfer employing two intense and time-delayed ultrashort laser pulses and different coupling schemes. For the purpose of interpretation, the coupled multilevel vibronic problem is reduced to a quasi-three-level system by averaging over the vibrational degree of freedom. It is shown that the vibrational dynamics becomes essential at high field intensities. Considering a 2-dimensional parameter space (intensity and delay time of the femtosecond laser pulses), a strong-field control landscape is constructed.


Mutational analysis of the lassa virus promoter.
The promoter sequences directing viral gene expression and genome replication of arenaviruses reside within the 3' and 5' termini of each RNA segment. The terminal 19 nucleotides at both ends are highly conserved among all arenavirus species and are almost completely complementary to each other. This study aimed at characterizing the Lassa virus promoter in detail. The relevance of each position in the promoter was studied by site-directed mutagenesis using the Lassa virus minireplicon system. The data indicate that the Lassa virus promoter functions as a duplex, regulates transcription and replication in a coordinated manner, and is composed of two functional elements, a sequence-specific region from residue 1 to 12 and a variable complementary region from residue 13 to 19. The first region appears to interact with the replication complex mainly via base-specific interactions, while in the second region solely base pairing between 3' and 5' promoter ends is important for promoter function.


Anticoagulant use and its effect on bleeding and complications in total knee arthroplasty.
Currently, there is very limited literature on the effect of long-term anticoagulants on total knee arthroplasty. The primary purpose of this study was to determine the effect of warfarin and clopidogrel on the transfusion rate, intra-operative blood loss, and postoperative blood loss for total knee arthroplasty. The secondary purpose was to determine their effect on post operative wound complications and length of stay. Data was collected retrospectively from medical charts between 2003-2008 and case matched to a control group. The patients on warfarin had a higher rate of blood transfusion, blood loss, and length of hospital stay compared to the clopidogrel and control groups.


Associated factors and effects of coronal vertebral wedging angle in thoracic adolescent idiopathic scoliosis.
Adolescent idiopathic scoliosis (AIS) causes vertebral wedging, but associated factors and the impact of vertebral wedging are still unknown. We investigated associated factors and effects of vertebral wedging in AIS using computed tomography (CT). Preoperative patients (n = 245) with Lenke types-1 and 2 were included. Vertebral wedging, lordosis, and rotation of the apical vertebra were measured by preoperative CT. Skeletal maturity and radiographic global alignment parameters were evaluated. Multiple regression analysis was performed on associated factors for vertebral wedging. Side-bending radiographs were evaluated using multiple regression analysis to calculate the percentage of reduction of Cobb angles to determine curve flexibility. The mean vertebral wedging angle was 6.8 ± 3.1°. Vertebral wedging angle was positively correlated with proximal thoracic (r = 0.40), main thoracic (r = 0.54), and thoracolumbar/lumbar curves (r = 0.38). By multiple regression, the central sacral vertical line (p = 0.039), sagittal vertical axis (p = 0.049), main thoracic curve (p = 0.008), and thoracolumbar/lumbar curve (p = 0.001) were significant factors for vertebral wedging. In traction and side-bending radiographs there were positive correlations between curve rigidity and the vertebral wedging angle (r = 0.60, r = 0.59, respectively). By multiple regression, thoracic kyphosis (p < 0.001), lumbar lordosis (p = 0.013), sacral slope (p = 0.006), vertebral wedging angle (p = 0.003), and vertebral rotation (p = 0.002) were significant factors for curve flexibility. Vertebral wedging angle was found to be highly correlated to coronal Cobb angle, with larger vertebral wedging indicating less flexibility.


New Insight into Mixing Fluoride and Chloride in Bioactive Silicate Glasses.
Adding fluoride into bioactive glasses leads to fluorapatite formation and a decrease in glass transition temperature. Recently, chloride has been introduced into glasses as an alternative to fluoride. The presence of the large chloride ion lowers glass crystallisation tendency and increases glass molar volume, which effectively facilitates glass degradation and bone-bonding apatite-like layer formation. However, there is no information regarding the effect of mixing fluoride and chloride on the glass structure and properties. This study aims to synthesize mixed fluoride and chloride containing bioactive glasses; investigate the structural role of fluoride and chloride and their effects on glass properties. The chloride content measurements reveal that 77-90% of chloride was retained in these Q2 type glasses. Glass transition temperature reduced markedly with an increase in CaX2 (X = F + Cl) content, while the glass molar volume increased. 29Si MAS-NMR results show that the incorporation of mixed fluoride and chloride did not cause significant change in the polymerization of the silicate network and no detectable concentration of Si-F/Cl bands were present. This agrees with 19F NMR spectra showing that F existed as F-Ca(n) species.


The Center for Epidemiologic Studies-Depression (CES-D) scale measures a continuum from well-being to depression: Testing two key predictions of positive clinical psychology.
Two core but untested predictions of Positive Clinical Psychology (PCP) are that (1) Many psychiatric problems can be understood as one end of bipolar continua with well-being, and (2) that reducing psychiatric symptoms will provide an equal (near linear) decrease in risk for several other psychiatric variables, irrespective of position on continua. We test these predictions in relation to a purported well-being/depression continuum, as measured by the Center for Epidemiologic Studies-Depression (CES-D), a popular measure of depressive experiences in research and clinical practice. A large (N=4138), diverse sample completed the CES-D, which contains a mixture of negatively worded and positively worded items (e.g., "I felt sad," "I enjoyed life"). The latter are conventionally reverse scored to compute a total score. We first examined whether purportedly separate well-being and depression CES-D factors can be reconceptualised as a bipolar well-being/depression continuum. We then characterised the (linear or nonlinear) form of the relationship between this continuum and other psychiatric variables. Both predictions were supported. When controlling for shared method bias amongst positively worded items, a single factor well-being/depression continuum underlies the CES-D. Baseline levels on this continuum are found to have near linear relationships with changes in anxiety symptoms, aggression, and substance misuse over time, demonstrating that moving from depression to well-being on the CES-D provides an equal decrease in risk for several other psychological problems irrespective of position on the continuum. The CES-D does not measure well-being as comprehensively as established scales of well-being. Results support calls for mental health services to jointly focus on increasing well-being and reducing distress, and point to the value of early intervention and instilling resilience in order to prevent people moving away from high levels of well-being.


Adrenocorticotropic hormone gel for patients with non-infectious uveitis.
To describe the potential role of adrenocorticotropic hormone (ACTH) gel treatment in patients with chronic non-infectious uveitis. We report the clinical course of three patients with bilateral, non-infectious anterior and intermediate uveitis, treated with ACTH gel for ≥12 months. All three patients had chronic and steroid-dependent ocular inflammation with subsequent development of ocular complications. Twice-weekly treatment with subcutaneous 80 unit/day ACTH gel was administered, and clinical outcome measures were observed. After a mean period of 14 months, all patients demonstrated significant improvement in disease activity, stable visual acuity, and an absence of side effects. Systemic steroids dosage was successfully reduced from a mean dose of 16 mg/day upon the initiation of ACTH gel treatment to 2 mg/day at last follow up. Subcutaneous ACTH gel has shown to be a safe and effective therapy in the management of non-infectious uveitis. Specifically, ACTH gel plays a role in refractory and steroid-dependent cases and in those who do not respond to or are unable to tolerate other immunomodulatory therapies.


Metastatic renal cell carcinoma to the small bowel 6 years postnephrectomy.
Renal cell carcinoma (RCC) is an unpredictable malignancy, with 25%-30% of patients developing metastatic disease. The most common sites of metastasis are the lung, bones, liver and brain, with small intestine metastasis being minimally reported in the literature. This report describes a case of small bowel obstruction caused by metastatic RCC in a male patient in his 60 s who had previously undergone a radical nephrectomy with adjuvant pembrolizumab therapy 6 years prior. The patient underwent a diagnostic laparoscopy converted to a laparotomy due to the complexity of the case. During surgical exploration, an enterectomy and end-to-end anastomosis were performed. This case emphasises the possibility of RCC metastasising to the small intestine, which may present with small bowel obstruction, while highlighting the importance of patient education for early detection to improve prognosis. Additionally, this report discusses treatment options for managing RCC metastasis to the small intestine.


Canard, homoclinic loop, and relaxation oscillations in a Lotka-Volterra system with Allee effect in predator population.
In this paper, we study the dynamics of a Lotka-Volterra model with an Allee effect, which is included in the predator population and has an abstract functional form. We classify the original system as a slow-fast system when the conversion rate and mortality of the predator population are relatively low compared to the prey population. In comparison to numerical simulation results that indicate at most three limit cycles in the system [Sen et al., J. Math. Biol. 84(1), 1-27 (2022)], we prove the uniqueness and stability of the slow-fast limit periodic set of the system in the two-scale framework. We also discuss canard explosion phenomena and homoclinic bifurcation. Furthermore, we use the enter-exit function to demonstrate the existence of relaxation oscillations. We construct a transition map to show the appearance of homoclinic loops including turning or jump points. To the best of our knowledge, the homoclinic loop of fast slow jump slow type, as classified by Dumortier, is uncommon. Our biological results demonstrate that under certain parameter conditions, population density does not change uniformly, but instead presents slow-fast periodic fluctuations. This phenomenon may explain sudden population density explosions in populations.